Very sensitive radioimmunoassay (RIA) for cyclic 3'5'-cytidine monophosphate (cCMP) has been developed using a very specific antisera raised against cCMP in rabbits. The RIA for cCMP is capable of measuring less than 10 femntomoles of cCMP. Since cyclic 3'5'-adenosine monophosphate (cAMP) cross reacts in this assay system, cAMP is separated from cCMP by chromatography Dowex 1-formate and small aliquots are collected in order to avoid interference of cAMP peak. With this method, it has not been possible to show the presence of cCMP in rat liver, human urine or mouse leukemia L1210 cells. Rat pancreas is the only tissue which appear to contain cCMP 0.5-1 pmole/g. It requires further confirmation. Whether cCMP plays a role in cell proliferation has yet to be established.